Exploiting Aromatic Interactions for b-Peptide Foldamer Helix Stabilization: A Significant Design Element

Mándity, István and Monsignori, Antonella and Fülöp, Lívia and Forró, Enikő and Fülöp, Ferenc (2014) Exploiting Aromatic Interactions for b-Peptide Foldamer Helix Stabilization: A Significant Design Element. CHEMISTRY-A EUROPEAN JOURNAL (20). pp. 4591-4597. ISSN 0947-6539

Text ChemEurJ2014.pdf - Published Version Restricted to Repository staff only Download (955kB) | Request a copy

Abstract

Tetrameric H10/12 helix stabilization was achieved by the application of aromatic side-chains in b-peptide oligomers by intramolecular backbone–side chain CH–p interactions. Because of the enlarged hydrophobic surface of the oligomers, a further aim was the investigation of the self-assembly in a polar medium for the b-peptide H10/12 helices. NMR, ECD, and molecular modeling results indicated that the oligomers formed by cis-[1S,2S]- or cis-[1R,2R]-1-amino- 1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (ATENAC) and cis-[1R,2S]- or cis-[1S,2R]-2-aminocyclohex-3-enecarboxylic acid (ACHEC) residues promote stable H10/12 helix formation with an alternating backbone configuration even at the tetrameric chain length. These results support the view that aromatic side-chains can be applied for helical structure stabilization. Importantly, this is the first observation of a stable H10/12 helix with tetrameric chain-length. The hydrophobically driven self-assembly was achieved for the helix-forming oligomers, seen as vesicles in transmission electron microscopy images. The self-association phenomenon, which supports the helical secondary structure of these oligomers, depends on the hydrophobic surface area, because a higher number of aromatic side-chains yielded larger vesicles. These results serve as an essential element for the design of helices relating to the H10/12 helix. Moreover, they open up a novel area for bioactive foldamer construction, while the hydrophobic area gained through the aromatic side-chains may yield important receptor–ligand interaction surfaces, which can provide amplified binding strength.

Actions (login required)

Edit Item